Analysis of CD97 expression and manipulation: antibody treatment but not gene targeting curtails granulocyte migration.
The heptahelical receptor CD97 is a defining member of the EGF-TM7 family of adhesion class receptors. In both humans and mice, CD97 isoforms are expressed with variable numbers of tandemly arranged N-terminal epidermal growth factor-like domains that facilitate interactions with distinct cellular ligands. Results from treatment of mice with mAbs in various disease models have suggested a role for CD97 in leukocyte trafficking. Here, we aimed to thoroughly characterize the expression profile of CD97, and delineate its biological function. To this end, we applied a novel polyclonal Ab, which is the first antiserum suitable for immunohistochemistry, and combined this analysis with the study of Cd97-lacZ knock-in mice. We show that similar to the situation in humans, hematopoietic, epithelial, endothelial, muscle, and fat cells expressed CD97. Despite this broad expression pattern, the Cd97(-/-) mouse that we created had no overt phenotype, except for a mild granulocytosis. Furthermore, granulocyte accumulation at sites of inflammation was normal in the absence of CD97. Interestingly, application of CD97 mAbs blocked granulocyte trafficking after thioglycollate-induced peritonitis in wild-type but not in knock-out mice. Hence, we conclude that CD97 mAbs actively induce an inhibitory effect that disturbs normal granulocyte trafficking, which is not perturbed by the absence of the molecule.
Veninga
Henrike
H
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Becker
Susann
S
Hoek
Robert M
RM
Wobus
Manja
M
Wandel
Elke
E
van der Kaa
Jos
J
van der Valk
Martin
M
de Vos
Alex F
AF
Haase
Hannelore
H
Owens
Bronwyn
B
van der Poll
Tom
T
van Lier
René A W
RA
Verbeek
J Sjef
JS
Aust
Gabriela
G
Hamann
Jörg
J
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000502:physiology; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D018390:Gene Targeting / Q000379:methods; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007964:Leukocytosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D043562:Receptors, G-Protein-Coupled; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
C490633:Adgre5 protein, mouse; D000906:Antibodies; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled